TABLE 3

Clinically observed drug-drug interactions (selection) with involvement of drug transporters

Transporter(s)	Inhibitor	Victim		Pharmacokinetic Changes of Victim Drug	Reference
Intestinal OATPs	Grapefruit juice	Fexofenadine	p.o.	↓ AUC, C_max	Dresser et al., 2002; Glaeser et al., 2007
	Grapefruit juice	Celiprolol	p.o.	↓ AUC, C_max	Lilja et al., 2003
	Orange juice	Aliskiren	p.o.	↓ AUC, C_max	Tapaninen et al., 2011
Hepatic OATPs	Cyclosporine	Pravastatin	p.o.	↑ AUC, C_max	Olbricht et al., 1997; Park et al., 2002; Hedman et al., 2004
	Cyclosporine	Rosuvastatin	p.o.	↑ AUC, C_max	Simonson et al., 2004
	Gemfibrozil	Pravastatin	p.o.	↑ AUC, C_max; ↓ Cl_r	Kyrklund et al., 2003
Renal OATs	Probenecid	Furosemide	i.v.	↑ AUC, C_max, t_max; ↓ Cl_r	Smith et al., 1980; Vree et al., 1995
	Probenecid	Furosemide	p.o.	↑ AUC; ↓ Cl_r	Smith et al., 1980; Vree et al., 1995
	Probenecid	Methotrexate	i.v.	↑ C_serum	Aherne et al., 1978
Renal cation transporters (OCT2, MATEs)	Cimetidine	Metformin	p.o.	↑ AUC, C_max; ↓ Cl_r	Somogyi et al., 1987
	Cimetidine	Ranitidine	p.o.	↑ AUC; ↓ Cl_r	van Crugten et al., 1986
	Cimetidine	Dofetilide	p.o.	↑ AUC, C_max; ↓ Cl_r	Abel et al., 2000
	Cimetidine	Pindolol	p.o.	↑ AUC, C_max; ↓ Cl_r	Somogyi et al., 1992
	Trimethoprim	Procainamide	p.o.	↑ AUC; ↓ Cl_r	Kosoglou et al., 1988
P-gp	Clarithromycin	Digoxin	p.o.	↑ AUC, C_max	Rengelshausen et al., 2003; Gurley et al., 2008
	Quinidine	Digoxin	i.v.	↑ C_serum; ↓ Cl_t, Cl_r	Leahey et al., 1981; Ochs et al., 1981; Schenck-Gustafsson and Dahlqvist, 1981; Fenster et al., 1982, 1984
	Rifampin	Digoxin	i.v.	↓ AUC, C_max; ↑ Cl_nr	Drescher et al., 2003; Greiner et al., 1999; Larsen et al., 2007; Gurley et al., 2008; Reitman et al., 2011
	Rifampin	Digoxin	p.o.	↓ AUC, C_max, F
	Rifampin	Talinolol	i.v.	↓ AUC, C_max; ↑ Cl_t	Westphal et al., 2000
	Rifampin	Talinolol	p.o.	↓ AUC, C_max, F; ↑ t_max, Cl_t	Westphal et al., 2000
	Ritonavir	Digoxin	i.v.	↑ AUC; ↓ Cl_t, Cl_r	Ding et al., 2004
	St John’s Wort	Digoxin	p.o.	↓ AUC, C_max, C_trough	Gurley et al., 2008; Johne et al., 1999
	St John’s Wort	Talinolol	i.v.	↑ Cl_nr	Schwarz et al., 2007
	St John’s Wort	Talinolol	p.o.	↓ AUC, F	Schwarz et al., 2007
BCRP	Topotecan	Elacridar	i.v.	↑ AUC	Kruijtzer et al., 2002
BCRP	Topotecan	Elacridar	p.o.	↑ AUC, C_max, F	Kruijtzer et al., 2002

↑, Significant increase; ↓, significant decrease; C_serum, serum concentration; C_trough, minimum plasma/serum concentration during steady state; Cl_r, renal clearance; Cl_nr, nonrenal clearance; F, bioavailability; NTCP, sodium/taurocholate cotransporting polypeptide (modified from Müller and Fromm, 2011).